Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Applicant’s election of Group I, corresponding to claims 38-45 and 47-49 following claim amendments without traverse in the reply filed on 01/15/2026 is acknowledged. Thus, amended claims 38-45, 47-49, and 53-55 are pending in this application; elected Group I, corresponding to claims 38-45 and 47-49 is now under consideration for examination; and claims 53-55 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Priority
Acknowledgment is made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is a 371 of PCT/KR2022/003365 filed on 03/10/2022 and claims the priority date of Korea applications: 10-2021-0031571 filed on 03/10/2021 and 10-2022-0026074 filed on 02/28/2022; however, no English translation of said foreign priority applications has been provided. Therefore, the priority date for instant claims under consideration is deemed to be the filing date of 371 of PCT/KR2022/003365 filed on 03/10/2022.
Information disclosure statement
The information disclosure statement (IDS) submitted on 09/09/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Objections-Specification/Drawings
The disclosure is objected to because of the following informalities: Drawings of the instant application do not have Figure numbers, corresponding Figure numbers are required for all the figures in the drawings. Appropriate correction is required.
Claim Objections
I. Claim 38 and claims 39-45 and 47-49 depending therefrom are objected to, due to the following informality: Claim 38 recites the phrase “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3.”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequences of SEQ ID NO: 1 and SEQ ID NO: 3 and thus makes it unclear; claim 38 and claims 39-45 and 47-49 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 1 and SEQ ID NO: 3, as well as the full length sequences. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to the nucleic acid sequences of SEQ ID NO: 1 and SEQ ID NO: 3, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 1 and SEQ ID NO: 3 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 38 and claims 39-45 and 47-49 depending therefrom is interpreted to encompass nucleotide sequences having any percentage homology/similarity to said sequences and having lipoxygenase and decarboxylase activities. Examiner suggests amending the claim to recite “…comprising the polynucleotide sequence of SEQ ID NO: 1 and comprising the polynucleotide of SEQ ID NO: 3”. For examination purposes claims 38-45 and 47-49 are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear.
II. Furthermore, claim 38 recites the phrase “represented by a nucleotide sequence SEQ ID NO: 1; and represented by a nucleotide sequence SEQ ID NO: 3”. The metes and bounds of the term “represented by” is not clear in the context of the claims. It is not clear to the examiner if the recited nucleic acid sequence has the polynucleotide sequence of SEQ ID NO: 1 and SEQ ID NO: 3? or is a representative member of a genus/merely exemplary. Examiner suggests amending the claim to make a direct reference to SEQ ID NO: 1 and SEQ ID NO: 3. Clarification and correction required.
III. For uniformity in formatting of claims, examiner suggest amending claims to recite “SEQ ID NO: 3”; and to correct a typographical error in claim 4, claim 4 recites “he…”, examiner suggests amending claim 4 to recite “The…” Correction is required.
Claim Rejections: 35 USC § 112(b)
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
I. Claim 38 and claims 39-45 and 47-49 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 38 is indefinite in the recitation of phrase “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3.”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequences of SEQ ID NO: 1 and SEQ ID NO: 3 and thus makes it unclear; claim 38 and claims 39-45 and 47-49 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 1 and SEQ ID NO: 3, as well as the full length sequences. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to the nucleic acid sequences of SEQ ID NO: 1 and SEQ ID NO: 3, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 1 and SEQ ID NO: 3 is encompassed within the scope of the claims. For examination purposes, claim 38 and claims 39-45 and 47-49 depending therefrom is interpreted to encompass nucleotide sequences having any percentage homology/similarity to said sequences and having lipoxygenase and decarboxylase activities. Examiner suggests amending the claim to recite “…comprising the polynucleotide sequence of SEQ ID NO: 1 and comprising the polynucleotide of SEQ ID NO: 3”. Appropriate correction is required.
II. Claims 39 and 47 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 39 and 47 are indefinite in the recitation of “derived”. The metes and bounds of the term “derived” is not clear in the context of the claim. It is not clear to the examiner what are the structures encompassed in “derived”? or is a representative member of a genus/merely exemplary. Furthermore, in claims 39 and 47 are indefinite in the recitation of “derived”; as written, one cannot determine if the term refers to ‘functions of several real variables” or ‘structural variables’ of claimed “derived” genes/polynucleotides (unlimited structures or structurally undefined molecules or functionally variable molecules and the extent of variability is unclear). The metes and bounds of the claims are unclear. For examination purposes, no patentable weight will be given to the terms. It is not clear to the examiner as to what the phrase “derived” means in the context of the above claims, is this synonymous with “obtained from specific source or having specific structures? or does it include natural and man-made variants of unlimited/undefined structures thereof from any source? Examiner suggests amending the claims to recite ”obtained from…”. Clarification and correction required.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
I. Claims 38-45 and 47-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 38-45 and 47-49, as interpreted are directed to encompass: any nucleic acid molecule encoding claimed genes “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3” in the claimed method (as in claim 1; as such, the term “a nucleotide sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1 and SEQ ID NO: 3 but any fragment/subsequences within SEQ ID NO: 1 and SEQ ID NO: 3; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, there is no structure associated with function with regard to the members of the genus of polynucleotides and encoded polypeptides in the claimed method i.e., “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3” (as in claim 1; as such, the term “a nucleotide sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1 and SEQ ID NO: 3 but any fragment/subsequences within SEQ ID NO: 1 and SEQ ID NO: 3; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
No information, beyond the characterization of isolated polynucleotides comprising the nucleic acid sequence of SEQ ID NO: 1 encoding a polypeptide having lipoxygenase activity and the nucleic acid sequence of SEQ ID NO: 3 and encoding a polypeptide having decarboxylase activity and an isolated recombinant microorganism comprising said encoding polynucleotides in a method for producing hydroxy fatty acids or hydroperoxyl fatty acids or secondary alcohols has been provided by the applicants’, which would indicate that they had possession of the claimed genus of encoding polynucleotides i.e., any nucleic acid molecule encoding claimed genes “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3” in the claimed method (as in claim 1; as such, the term “a nucleotide sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1 and SEQ ID NO: 3 but any fragment/subsequences within SEQ ID NO: 1 and SEQ ID NO: 3; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
The claimed genus of encoding polynucleotides is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of encoding polynucleotides is adequately described by the disclosure of the structures of the nucleic acid sequence of SEQ ID NO: 1 encoding a polypeptide having lipoxygenase activity and the nucleic acid molecule of SEQ ID NO: 3 encoding a polypeptide having decarboxylase activity, since one could use structural homology to isolate those encoding polypeptides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (i) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(ii) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(iii) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase.
As the claimed genera encoding polynucleotides include widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants’ are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 38-45 and 47-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement, because the specification, while being enabling for the characterization of isolated polynucleotides comprising the nucleic acid sequence of SEQ ID NO: 1 encoding a polypeptide having lipoxygenase activity and the nucleic acid sequence of SEQ ID NO: 3 and encoding a polypeptide having decarboxylase activity and an isolated recombinant microorganism comprising said encoding polynucleotides in a method for producing hydroxy fatty acids or hydroperoxyl fatty acids or secondary alcohols; does not reasonably provide enablement for genus of encoding polynucleotides i.e., any nucleic acid molecule encoding claimed genes “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3” in the claimed method (as in claim 1; as such, the term “a nucleotide sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1 and SEQ ID NO: 3 but any fragment/subsequences within SEQ ID NO: 1 and SEQ ID NO: 3; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The breadth of claims includes overly broad genus, applicants’ disclose no direction or guidance on how to design and make any polypeptide and the encoding polynucleotide of undefined structure having desired activity as noted in the breadth above. Thus, instant specification and prior art failed to describe how to make and use the claimed genus of encoding polynucleotides sufficiently. Although, it is possible to display and create any protein structure in computer (in silico) and manipulate in any possible way, such as inserting any amino acid(s) into preexisting three-dimensional scaffold; the creation of desired catalytic/biologic activity in a solution is highly unpredictable.
According to MPEP § 2164.02: “All questions of enablement are evaluated against the claimed subject matter. The focus of the examination inquiry is whether everything within the scope of the claim is enabled.”; “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the invention need be disclosed. In fact, what is well-known is best omitted. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). All that is necessary is that one skilled in the art be able to practice the claimed invention, given the level of knowledge and skill in the art. Further the scope of enablement must only bear a “reasonable correlation” to the scope of the claims. See, e.g., In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”; and “As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. > AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); < In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged “pioneer status” of invention irrelevant to enablement determination).”
Instant claims are so broad such that, instant disclosure of instant specification and a general knowledge in the art are not commensurate with the scope of instant claims for one skilled in the art to make and use claimed invention without undue experimentation. As noted above, the breadth of instant claims encompass an overly broad genus of undefined structure including variants, mutants and homologs.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability of the prior art in regard to structural variability and its effect on function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of any nucleic acid molecule encoding claimed genes “a lipoxygenase gene represented by a nucleotide sequence SEQ ID NO: 1 and a decarboxylase gene represented by a nucleotide sequence of SEQ ID NO: 3” in the claimed method (as in claim 1; as such, the term “a nucleotide sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1 and SEQ ID NO: 3 but any fragment/subsequences within SEQ ID NO: 1 and SEQ ID NO: 3; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation), is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
Art of Interest
Based on the granted priority for the instant application, Cha et al., (ACS Sustainable Chem. Eng., 2021, Vol. 9: 10837-10845; published 08/02/2021) disclose a recombinant cell that expresses genes encoding a lipoxygenase gene and a decarboxylase gene in a method for producing hydroxy fatty acids or hydroperoxyl fatty acids or secondary alcohols comprising culturing said recombinant cell and as a whole-cell biocatalyst. However, the cited art is not used in any rejection, because said reference does not disclose isolated polynucleotides comprising the nucleic acid sequence of SEQ ID NO: 1 encoding a polypeptide having lipoxygenase activity and the nucleic acid sequence of SEQ ID NO: 3 and encoding a polypeptide having decarboxylase activity and an isolated recombinant microorganism comprising said encoding polynucleotides in a method for producing hydroxy fatty acids or hydroperoxyl fatty acids or secondary alcohols.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652